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首页> 外文期刊>Neuron >Gamma Oscillation Dysfunction in mPFC Leads to Social Deficits in Neuroligin 3 R451C Knockin Mice
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Gamma Oscillation Dysfunction in mPFC Leads to Social Deficits in Neuroligin 3 R451C Knockin Mice

机译:MPFC中的伽玛振荡功能障碍导致神经源素3R451C Knockin小鼠的社会缺陷

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摘要

Neuroligins (NLs) are critical for synapse formation and function. NL3 R451C is an autism-associated mutation. NL3 R451C knockin (KI) mice exhibit autistic behavioral abnormalities, including social novelty deficits. However, neither the brain regions involved in social novelty nor the underlying mechanisms are clearly understood. Here, we found decreased excitability of fast-spiking interneurons and dysfunction of gamma oscillation in the medial prefrontal cortex (mPFC), which contributed to the social novelty deficit in the KI mice. Neuronal firing rates and phase-coding abnormalities were also detected in the KI mice during social interactions. Interestingly, optogenetic stimulation of parvalbumin interneurons in the mPFC at 40 Hz nested at 8 Hz positively modulated the social behaviors of mice and rescued the social novelty deficit in the KI mice. Our findings suggest that gamma oscillation dysfunction in the mPFC leads to social deficits in autism, and manipulating mPFC PV interneurons may reverse the deficits in adulthood.
机译:神经源素(NLS)对于突触形成和功能至关重要。 NL3 R451C是一种自闭症相关的突变。 NL3 R451C Knockin(Ki)小鼠表现出自闭症行为异常,包括社会新奇赤字。然而,涉及社会新颖性和潜在机制的大脑区域都没有明白。在这里,我们发现在内侧前额叶皮质(MPFC)中的快速尖峰间的兴奋性和γ振荡功能障碍的兴奋性降低,这导致了KI小鼠的社会新奇缺陷。在社交互动期间,在Ki小鼠中也检测到神经元烧制率和相位编码异常。有趣的是,在MPFC中的40 Hz在8赫兹的MPFC中对Parvalbumise interdulation的致敏刺激积极调制了小鼠的社会行为,并救出了Ki小鼠的社会新奇缺陷。我们的研究结果表明,MPFC中的Gamma振荡功能障碍导致自闭症中的社会赤字,操纵MPFC PV Interneurons可能会扭转成年期的赤字。

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  • 来源
    《Neuron》 |2018年第6期|共15页
  • 作者单位

    Zhejiang Univ Sch Med Collaborat Innovat Ctr Brain Sci Key Lab Med Neurobiol Minist Hlth China;

    Zhejiang Univ Sch Med Collaborat Innovat Ctr Brain Sci Key Lab Med Neurobiol Minist Hlth China;

    Zhejiang Univ Sch Med Collaborat Innovat Ctr Brain Sci Key Lab Med Neurobiol Minist Hlth China;

    Zhejiang Univ Sch Med Collaborat Innovat Ctr Brain Sci Key Lab Med Neurobiol Minist Hlth China;

    Zhejiang Univ Sch Med Collaborat Innovat Ctr Brain Sci Key Lab Med Neurobiol Minist Hlth China;

    Zhejiang Univ Sch Med Collaborat Innovat Ctr Brain Sci Key Lab Med Neurobiol Minist Hlth China;

    Zhejiang Univ Sch Med Collaborat Innovat Ctr Brain Sci Key Lab Med Neurobiol Minist Hlth China;

    Zhejiang Univ Sch Med Collaborat Innovat Ctr Brain Sci Key Lab Med Neurobiol Minist Hlth China;

    Zhejiang Univ Sch Med Collaborat Innovat Ctr Brain Sci Key Lab Med Neurobiol Minist Hlth China;

    Hong Kong Univ Sci &

    Technol Div Biomed Engn Div Life Sci Kowloon Hong Kong Peoples R China;

    MIT Dept Brain &

    Cognit Sci E25-618 Cambridge MA 02139 USA;

    Zhejiang Univ Sch Med Collaborat Innovat Ctr Brain Sci Key Lab Med Neurobiol Minist Hlth China;

    Zhejiang Univ Sch Med Collaborat Innovat Ctr Brain Sci Key Lab Med Neurobiol Minist Hlth China;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 神经病学;
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